The racemic (+/−)-cis- and trans-isomers of 2-methyl-6-nundecylpiperidine are known as isosolenopsin A and solenopsin A, respectively. Arbiser et al. report solenopsin is an inhibitor of phosphatidylinositol-3-kinase signaling and angiogenesis. See Blood (2007) 109, 560-565.
The serine/threonine kinase c-Akt-1, or protein kinase Bα (PKB), is the cellular homolog of a transforming oncogene initially isolated from a lymphoma. Akt is a downstream target of phosphatidylinositol-3-kinase (PI3K), a family of at least 4 different enzymes, with the prototypical PI3K heterodimer consisting of a p85 (regulatory) and a p110 (catalytic) subunit. The PI3K/Akt pathway is involved in the regulation of diverse cellular functions including proliferation, cytoskeletal organization, survival, and malignant transformation. Upon binding of PI3K products to its pleckstrin homology domain, Akt is translocated to the plasma membrane where it is activated by upstream phosphorylated kinases, including PI3K-dependent kinases 1 and 2 (PDK1 and PDK2) and mammalian target of rapamycin complex 2 (mTORC2). The PI3K/Akt pathway is stimulated by numerous receptor tyrosine kinases and oncogenes, including receptors for insulin-like growth factor 1 (IGF-1), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), ras, Her2/neu, and polyoma middle T oncogenes. Because Akt plays a central role in regulating apoptosis, angiogenesis, and metabolism of cells, Akt is an attractive pharmacologic target for the treatment of cancer and inflammation. Thus, there is a need to identify compound that target the PI3K/Akt pathway.
Yi et al. report that fire ant venom alkaloid, isosolenopsin A, is a potent and selective inhibitor of neuronal nitric oxide synthase. Int J Toxicol, 2003, 22(2):81-6. Chen et al., report the reduction of venom alkaloids. J Agric Food Chem, 2010, 58(22):11534-42. See also Chen et al., Chem Biodivers, 2012, 9(4):702-13.
References cited herein are not an admission of prior art.